Aloesin ameliorates hypoxic-ischemic brain damage in neonatal mice by suppressing TLR4-mediated neuroinflammation.

Publisher: John Wiley and Sons Ltd Country of Publication: England NLM ID: 101635460 Publication Model: Print Cited Medium: Internet ISSN: 2050-4527 (Electronic) Linking ISSN: 20504527 NLM ISO Abbreviation: Immun Inflamm Dis Subsets: MEDLINE

Original Publication: [Oxford] : John Wiley and Sons Ltd, [2013]-

Toll-Like Receptor 4*/metabolism ; Hypoxia-Ischemia, Brain*/drug therapy ; Hypoxia-Ischemia, Brain*/metabolism ; Hypoxia-Ischemia, Brain*/pathology ; Animals, Newborn* ; Neuroprotective Agents*/pharmacology ; Neuroprotective Agents*/therapeutic use ; Neuroinflammatory Diseases*/drug therapy ; Neuroinflammatory Diseases*/etiology ; Neuroinflammatory Diseases*/pathology ; Neuroinflammatory Diseases*/metabolism; Animals ; Mice ; Mice, Inbred ICR ; Disease Models, Animal ; Signal Transduction/drug effects ; Apoptosis/drug effects ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Molecular Docking Simulation

Background: At present, neonatal hypoxic-ischemic encephalopathy (HIE), especially moderate to severe HIE, is a challenging disease for neonatologists to treat, and new alternative/complementary treatments are urgently needed. The neuroinflammatory cascade triggered by hypoxia-ischemia (HI) insult is one of the core pathological mechanisms of HIE. Early inhibition of neuroinflammation provides long-term neuroprotection. Plant-derived monomers have impressive anti-inflammatory effects. Aloesin (ALO) has been shown to have significant anti-inflammatory and antioxidant effects in diseases such as ulcerative colitis, but its role in HIE is unclear. To this end, we conducted a series of experiments to explore the potential mechanism of ALO in preventing and treating brain damage caused by HI insult.
Materials and Methods: Hypoxic-ischemic brain damage (HIBD) was induced in 7-day-old Institute of Cancer Research (ICR) mice, which were then treated with 20 mg/kg ALO. The neuroprotective effects of ALO on HIBD and the underlying mechanism were evaluated through neurobehavioral testing, infarct size measurement, apoptosis detection, protein and messenger RNA level determination, immunofluorescence, and molecular docking.
Results: ALO alleviated the long-term neurobehavioral deficits caused by HI insult; reduced the extent of cerebral infarction; inhibited cell apoptosis; decreased the levels of the inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α; activated microglia and astrocytes; and downregulated the protein expression of members in the TLR4 signaling pathway. In addition, molecular docking showed that ALO can bind stably to TLR4.
Conclusion: ALO ameliorated HIBD in neonatal mice by inhibiting the neuroinflammatory response mediated by TLR4 signaling.
(© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

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202212826 The Science and Technology Planed Projects of Jiangxi Provincial Health Commission

Keywords: Aloesin; TLR4; hypoxic‐ischemic brain damage; neuroinflammation

0 (Toll-Like Receptor 4)
0 (Tlr4 protein, mouse)
0 (Neuroprotective Agents)
0 (Anti-Inflammatory Agents)

Date Created: 20240618 Date Completed: 20240618 Latest Revision: 20240628

20240628

PMC11184644

10.1002/iid3.1320

38888378